Targeting colon cancer cell NF-κB promotes an anti-tumour M1-like macrophage phenotype and inhibits peritoneal metastasis (Oncogene (2014), 1–12 )

報告日期: 2015/03/20
報告時間: 17:10/18:00
報告學生: 陳智源(以英文報告)
講評老師: 王育民
附件下載: 下載[1477-1425858585-1.pdf] 

Targeting colon cancer cell NFκB promotes an anti-tumor M1-like macrophage phenotype and inhibits peritoneal metastasis

Oncogene 2014, 1-12.

Commentator: Wang Yu-ming , Ph.D

Speaker: Chan Zhi-yuan

Date: 2015/3/20

Abstract

  Metastatic colorectal cancer poses a significant health problem both in terms of its poor prognosis and high incidence. When colorectal cancer spread to liver and peritoneal is associated with patient poor outcome. The tumor microenvironment plays an important role in cancer metastasis, and attracted many research interest to study the interaction between tumor cells and the local milieu. Growing evidence suggests that immune cells, in particular tumor-associated macrophages (TAMs), in the microenvironment are important actors in the metastatic capacity of tumors. In malignant tumors, TAMs mostly resemble an M2-like phenotype, which increases angiogenesis and growth and suppresses anti-tumor immunity [1]. However, very few targetable tumor-specific factors that regulate the phenotype of TAMs have been identified so far. Nuclear factor-кB (NF-κB) transcription factors have central roles in physiological and pathological processes, including inflammatory responses and cell survival. Activation of NF-кB by pro-inflammatory cytokines suggests that NF-кB may be an important link between the processes of inflammation and cancer. However, that the role of NF-кB in the development of cancer is complex. Recent work has highlighted the role of NF-кB in regulating colon cancer cell anoikis, suggesting that NF-кB might also be important in promoting peritoneal metastasis [2]. In this article, authors demonstrated that NF-кB signaling promotes peritoneal metastasis of colon cancer cells that is dependent on the presence of macrophages. Targeting NF-κB induced an M1-like macrophage phenotype, which significantly reduced peritoneal metastasis in vivo. Enhanced M1-like phenotype was associated with a greater frequency of intratumoral activated CD4+ and CD8+ T cells, decreased angiogenesis, increased iNOS expression in infiltrating mononuclear cells and increased intratumoral apoptosis.

Reference

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  2. Toruner M, Fernandez-Zapico M, Sha JJ et al. Antianoikis effect of nuclear factor-kappa B through up-regulated expression of osteoprotegerin, BCL-2, and IAP-1. Journal of Biological Chemistry 2006; 281: 8686-8696.